NM_001282116.2:c.1772C>A

Variant names:

• chr9-3257033-G-T
• NM_001282116.2:c.1772C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001282116.2(RFX3):​c.1772C>A​(p.Pro591His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RFX3 NM_001282116.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0

Genes affected

RFX3 (HGNC:9984): (regulatory factor X3) This gene is a member of the regulatory factor X gene family, which encodes transcription factors that contain a highly-conserved winged helix DNA binding domain. The protein encoded by this gene is structurally related to regulatory factors X1, X2, X4, and X5. It is a transcriptional activator that can bind DNA as a monomer or as a heterodimer with other RFX family members. Multiple transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.756

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFX3	NM_001282116.2	c.1772C>A	p.Pro591His	missense_variant	Exon 14 of 17	ENST00000617270.5	NP_001269045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFX3	ENST00000617270.5	c.1772C>A	p.Pro591His	missense_variant	Exon 14 of 17	2	NM_001282116.2	ENSP00000482598.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.66	D;D;.;.;T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	.;D;D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.76	D;D;D;D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.1	M;M;M;.;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-6.5	D;.;D;D;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D;.;D;T;D
Sift4G	Uncertain	0.0040	D;D;D;D;D
Polyphen		0.94	P;P;D;.;.
Vest4		0.68
MutPred		0.38		Loss of glycosylation at P591 (P = 0.0323);Loss of glycosylation at P591 (P = 0.0323);Loss of glycosylation at P591 (P = 0.0323);.;.;
MVP		0.28
MPC		2.6
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.73
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-3257033;